Simple trimerization of 2,3-butanedione yielding a selective reagent for the modification of arginine in proteins

Yankeelov, John A.; Mitchell, Carolyn Dempsey; Crawford, Thomas H.

doi:10.1021/ja01008a056

Cited by 79 publications

(25 citation statements)

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“…Activity also remained after treatment with diacetyl trimer (30). Treatment with o-phthalaldehyde (31) as well as photooxidation (32) of the toxin resulted in a complete loss of the toxic activity.…”

mentioning

confidence: 99%

Investigations into the relationship between structure and function of diphtheria toxin.

Everse¹,

Lappi²,

Beglau³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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Studies on the structure-function relationship of diphtheria toxin are reported. New methods are described for the preparation of pure intact ("unnicked") molecule (or the A chain) to enter the cell (11). The complete amino acid sequence of the A chain has recently become available (12). A recent report by Iglewski and Rittenberg (13) indicated that protein synthesis in Ehrlich-Lettr6 ascites carcinoma cells is much more sensitive to the action of diphtheria toxin than that in normal mouse spleen cells, and that Ehrlich-Lettre tumors regressed in mice following an injection of the affected mice with diphtheria toxin. A difference in sensitivity to diphtheria toxin was also found in human breast carcinoma cells as compared to normal human cells. These observations suggest that diphtheria toxin may prove to be a useful anti-cancer agent, although more recent data indicate that the difference in sensitivity of tumor cells to toxin as compared to normal cells may not be as large as originally thought (14,15).It is therefore of considerable interest to us to investigate the mechanism of action of diphtheria toxin in greater detail. More specifically, we are trying to gain further information concerning the amino acid residues of the toxin that are essential for its activity, and to investigate the mechanism by which diphtheria toxin enters the cell. Some of the results obtained during this investigation are presented in this paper. MATERIALS AND METHODS Materials

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mentioning

confidence: 99%

Investigations into the relationship between structure and function of diphtheria toxin.

Everse¹,

Lappi²,

Beglau³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…Effect of diacetyl trimer. Diacetyl trimer is selective for the modification of arginine in proteins (GROSSBERG and PRESSMAN, 1968;MARSCHEL and BODLEY, 1980;YANKEELOV et al, 1968). The presence of L-glu was essential for modifying the guanidino group of arginine residue.…”

Section: Discussionmentioning

confidence: 99%

Effects of chemical modification on the L-glutamate receptors on the Onchidium neuron.

1983

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In the G-H cells of Onchidium oesophageal ganglia, L-glutamate (L-glu) elicited hyperpolarizations caused by an increase in potassium permeability. To identify the chemical groups of the structure of the L-glu receptor, which is involved in the L-glu response, the effects of chemical modifications were studied. Modifications of SH, guanidino, COOH, or NH2 groups depressed L-glu response. The modification of other polar amino acid residues and phospholipids, however, did not have an effect on the L-glu responses.

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“…Affinity chromatography and 31 P NMR studies of flavonol 3-ST demonstrated the involvement of Lys 59 , Arg 11 , and Arg 277 in PAPS binding (6). Point mutations and […”

Section: Sulfotransferases (Sts)mentioning

confidence: 99%

“…1). BD has been used for the characterization of Arg residues in various enzymes (31)(32)(33)(34). Because borate is necessary to form a stable adduct (Fig.…”

Section: Chemical Inactivation Of Sult1a1 By Arginine Residue-specifimentioning

confidence: 99%

Arginine Residues in the Active Site of Human Phenol Sulfotransferase (SULT1A1)

Chen

2003

Journal of Biological Chemistry

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Cytosolic sulfotransferases (STs) catalyze the sulfation of hydroxyl containing compounds. Human phenol sulfotransferase (SULT1A1) is the major human ST that catalyzes the sulfation of simple phenols. Because of its broad substrate specificity and lack of endogenous substrates, the biological function of SULT1A1 is believed to be an important detoxification enzyme. In this report, amino acid modification, computer structure modeling, and site-directed mutagenesis were used for studies of Arg residues in the active site of SULT1A1. The Argspecific modification reagent, 2,3-butanedione, inactivated SULT1A1 in an efficient, time-and concentrationdependent manner, suggesting Arg residues play an important role in the catalytic activity of SULT1A1. , and the negative charge on 3-phosphate is the primary force stabilizing the specific binding of PAPS. Sulfotransferases (STs)1 catalyze the sulfation of hydroxylcontaining molecules. The substrate specificities of STs are very broad. Most hydroxyl groups in phenols, alcohols, and N-substituted hydroxylamines are substrates for one of the ST isoforms. The co-substrate for sulfation of all STs is adenosine 3Ј-phosphate 5Ј-phosphosulfate (PAPS). Sulfation (sulfuryl transfer) is widely observed in various biological processes. Various biological signaling molecules, including hormones, neurotransmitters, peptides, and proteins, can be sulfated to alter biological activity. STs also catalyze the sulfation of a broad range of xenobiotics. Sulfation of drugs and xenobiotics is mainly associated with detoxification: biotransformation of a relatively hydrophobic xenobiotic into a more water-soluble sulfuric ester that is readily excreted. However, there are numerous important exceptions wherein the formation of chemically reactive sulfuric esters is an essential step in the metabolic pathways leading to toxic or carcinogenic responses. Detoxification or bioactivation is highly dependent on the electrophilic reactivity of the individual sulfuric ester products formed. Most sulfation products are stable enough for excretion, while other sulfuric ester products can be reactive toward nucleophilic sites on DNA, RNA, and protein, and so become involved in the initiation of carcinogenesis and other toxic responses.Structure-activity relationship studies of STs started in the 1980s. Protein sequence alignments of the different STs have revealed two highly conserved regions, one (PKSGTTW) in the N-terminal region and one (RKGXXGDWK) in the C-terminal region (1). Since all STs use the same sulfuryl donor, it was speculated that these two regions were involved in PAPS binding (2, 3). Affinity labeling of rat liver aryl ST-IV identified a peptide sequence in the PAPS-binding site, which is in close proximity to the highly conserved sequence in the N-terminal region (4). Site-directed mutagenesis and [35 S]PAPS affinity labeling studies of flavonol 3-ST have supported that the two regions mentioned above are involved in PAPS binding (5). Affinity chromatography and 31 P NMR studies of flavon...

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Simple trimerization of 2,3-butanedione yielding a selective reagent for the modification of arginine in proteins

Cited by 79 publications

References 1 publication

Investigations into the relationship between structure and function of diphtheria toxin.

Investigations into the relationship between structure and function of diphtheria toxin.

Effects of chemical modification on the L-glutamate receptors on the Onchidium neuron.

Arginine Residues in the Active Site of Human Phenol Sulfotransferase (SULT1A1)

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